Statins for Primary Prevention of Cardiovascular Disease — The JUPITER Study

One of 2008’s most hotly debated studies has the potential to change prevention recommendations for millions of Americans. In the industry-sponsored JUPITER study, researchers investigated the role of statins in primary prevention when patients’ cholesterol levels were not markedly high but high-sensitivity C-reactive protein (hsCRP) was elevated (JW Nov 18 2008). Nearly 18,000 subjects (ages: men, ≥50; women, ≥60) without known cardiovascular (CV) disease and with normal LDL-cholesterol levels (<130 mg/dL), but with high hsCRP levels (≥2 mg/L), were randomized to receive daily rosuvastatin (Crestor; 20 mg) or placebo. Extensive exclusion criteria eliminated many patients (e.g., those with diabetes, uncontrolled hypertension, or various other chronic diseases; those who used cholesterol-lowering drugs).

After a median follow-up of 1.9 years (the trial was stopped early, due to markedly positive results for rosuvastatin), rosuvastatin lowered LDL-cholesterol levels by a mean of 50% and hsCRP levels by 37%. Incidence of the primary endpoint (first major cardiovascular event, including unstable angina, myocardial infarction, stroke, arterial revascularization, or death from cardiovascular causes) was significantly lower in the rosuvastatin group than in the placebo group (hazard ratio, 0.56), as was overall mortality (HR, 0.8). For every 1000 patients who received rosuvastatin for 1 year, roughly six fewer primary-endpoint events and three fewer deaths occurred. Incidences of physician-reported diabetes and glycosylated hemoglobin levels were both significantly higher in the rosuvastatin group than in the placebo group.

So, where do we go from here? Statins lowered the rate of adverse CV events in this large study of apparently healthy subjects who were at CV risk because of high hsCRP levels; however, in an accompanying editorial, the author notes that the absolute effect size was relatively modest and that the higher incidence of diabetes and lack of long-term data on hazards of therapy are worrisome. Nonetheless, these data almost certainly will prompt review of current guidelines on use of statins in primary prevention, as well as generate a flurry of calls to physicians about hsCRP testing. Some media reports on JUPITER have couched the study results as supporting widespread use of hsCRP testing, but the editorialist reminds us that this is a randomized trial of statin therapy, not of hsCRP testing, and he advocates selective rather than routine CRP testing (JW Nov 18 2008).